The Pertussis resurgence: putting together the pieces of the puzzle

Abstract

Pertussis incidence is rising in almost every country where acellular pertussis (aP) vaccines have been introduced, and is occurring across all age groups from infancy to adulthood. The key question is why? While several known factors such as waning of immunity, detection bias due to more sensitive tests and higher awareness of the disease among practitioners, and evolutionary shifts among B. pertussis all likely contribute, collectively, these do not adequately explain the existing epidemiologic data, suggesting that additional factors also contribute. Key amongst these is recent data indicating that the immune responses induced by aP vaccines differ fundamentally from those induced by the whole cell pertussis (wP) vaccines, and do not lead to mucosal immunity. If so, it appears likely that differences in how the two categories of vaccines work, may be pivotal to our overall understanding of the pertussis resurgence.

Keywords: Acellular pertussis vaccine; Asymptomatic transmission; Epidemiologic modeling; Pertussis; Pertussis vaccines; Resurgence; Review.

Fig. 1

Pertussis cases in the US, 1940–2012. Data are from the Centers for Disease Control and Prevention via the National Notifiable Diseases Surveillance System

Fig. 2

Outcomes of experimental exposure to pertussis among aP or wP vaccinated or unvaccinated infant baboons. Three groups of infant baboons were exposed to infectious aerosols of B. pertussis: unvaccinated control animals; animals vaccinated using acellular pertussis vaccines; animals vaccinated using whole cell pertussis vaccines. The vaccinated animals completed a full vaccination series and were allowed time to fully seroconvert before exposure. The two vaccinated groups of animals both remained asymptomatic, whereas the unvaccinated animals developed clinical disease. However, nasopharyngeal sampling of the three groups showed that the aP and unvaccinated animals both were infected with similar densities of pertussis bacteria and for similar durations. By contrast, the wP vaccinated animals were more resistant to carriage, and carried bacteria for shorter periods. This showed that wP and aP vaccinations induce very different mucosal immune responses, with the former protecting against infection and disease, and the latter only preventing clinical disease, but not infection

Fig. 3

Outcome of exposure to infected animal by vaccination status. Here, an infected unvaccinated animal was co-housed with three initially uninfected animals, one of which was unvaccinated, while the other two had received aP vaccinations. All three animals became infected based on nasopharyngeal sampling, though only the unvaccinated animal showed signs of clinical illness. This showed that infection due to exposure to an infected animal can transmit B. pertussis (a more realistic model than exposure to aerosols). But again, while aP vaccinations blocked clinical disease, they did not prevent infection

Fig. 4

Infections from an asymptomatic vaccinated to unvaccinated animal. The first experiment showed that an unvaccinated but infected animal is capable of infecting an aP vaccinated animal. This experiment approaches this dynamic in reverse: here an aP vaccinated animal was infected with B. pertussis and then co-housed with an unvaccinated animal. Despite being asymptomatic, the aP vaccinated animal quickly infected the vaccine naïve control animal, who developed clinical disease as well as nasopharyngeal carriage showing that infection had occurred. This proved that, despite being symptom free, aP vaccinated animals can become infected with pertussis, and are able to transmit to unvaccinated animals. In other words, aP vaccination only prevented clinical disease, but did not prevent animals from being infectious and contributing to chains of transmission